Khalil Shikaki was born on September 8, 1953 in the Gaza Strip city of Rafiah. He enrolled at Bir Zeit University in the West Bank in 1971 before transferring to the American University in Beirut, where he earned both bachelor's (1975) and master's (1977) degrees in International Relations and Middle Eastern Studies. Shikaki then worked for General Motors in Kuwait from 1977 to 1980, at which time he moved to the U.S. and enrolled at Columbia University, obtaining a Middle East Institute Certificate in 1983 and a Ph.D. in 1985.

Shikaki was hired as a USF professor in 1991, but when An-Najjah University reopened later that year, he tried to return to his previous post there. However, Israeli authorities—citing intelligence which indicated that Shikaki's brother, Fathi Shikaki, was the head of PIJ—denied Khalil Shikaki permission to enter the country. Eventually, though, Shikaki persuaded the U.S. State Department to pressure Israel into granting him entry, which Israel ultimately did.

In the 2005 terrorism trial of Sami Al-Arian, prosecutors presented evidence proving conclusively that Shikaki was a key player in PIJ's American arm; that in the early 1990s he had received numerous payments and money transfers from accounts belonging to Al-Arian and groups affiliated with him; that he had held and distributed money in the West Bank for Al-Arian associates; that he had maintained an ongoing and friendly relationship with high-ranking PIJ operative Ramadan Abdullah Shallah, who advocated the use of “armed struggle” and “martyrdom” operations against Israel; and that he had collaborated with his brother (Fathi Shikaki) and Shallah in severalprojects, including one revolving around Hamas political bureau chief Mousa Abu Marzook.

Khalil Shikaki was a guest speaker at the second, third, and fourth annual conferences of the PIJ front group Islamic Committee for Palestine (ICP), events which were held in Chicago from 1989-91. Also speaking at these gatherings were such notables as:

In June 1991, Khalil Shikaki, Sami Al-Arian, and Bashir Nafi met with representatives of USF's Middle East Studies Committee to discuss the possibility of engaging in future cooperative efforts. Shikaki became an adjunct professor in the University's Middle East Studies Department soon thereafter, and the agreement he had helped negotiate was formally signed in 1992.In July 1991 Shikaki delivered a speech at a Herndon, Virginia conference titled “The Islamic Movement in the Shadow of International Change and Crisis in the Gulf,” sponsored by the United Association for Studies and Research (UASR)—an organization known for its publication of pro-Hamas literature. Other speakers included Sami Al-Arian; Ramadan Abdullah Shallah; Muhammad al-Asi; Ishaq al-Farhan, a leader of the militant Islamic Jordan Action Front; Kamal al-Hilbawi, a Muslim Brotherhood spokesman who has advocated suicide bombings and armed attacks against American targets; Taha Jaber al-Alwani, who has served as an official with numerous Muslim Brotherhood-affiliated organizations; Mousa Abu Marzook, a Hamas operative and Holy Land Foundation founder; and Ahmed Bin Yousef, the pro-Hamas executive director of UASR.

In 1993 in Nablus, Khalil Shikaki founded the Center for Palestine Research. In late January 1995, shortly after President Bill Clinton had issued an executive order outlawing all transactions with PIJ, Shikaki cut his ties to the organization. According to the Investigative Project on Terrorism (IPT), “There is no evidence that Shikaki has been involved with or connected with any radical Islamic group since 1995.” But IPT director Steven Emerson emphasizes that in prior years, “Shikaki was pivotal to the creation of a terror network.”

In 2004 Shikaki, who has long taken pains to publicly portray himself a moderate, addressed the annual conference of the pro-Israel lobby AIPAC. He also spoke to a number of Jewish organizations and synagogues in the Greater Boston area following his January 2006 appointment as a Senior Fellow at Brandeis University's Crown Center for Middle East Studies—a post he continues to hold.

In a January 2006 working paper titled With Hamas in Power: Impact of Palestinian Domestic Developments on Options for the Peace Process, Shikaki urged Israel to free the incarcerated former Fatah leader Marwan Barghouti, who in 2004 had been convicted on five counts of murder and one count of attempted murder. Shikaki wrote that “Israel needs to release Barghouti” with the aim of “improving relations with the Palestinians” and “unifying the 'young guard' [of Fatah] under his leadership while cementing his relationship with [President Mahmoud] Abbas.” Unfazed by the harsh criticisms generated by his recommendation, Shikaki subsequently elaborated: “Mr. Barghouti is the most popular Palestinian leader at this time. He is perceived by the public as clean and patriotic. He can defeat any potential Hamas leader when it is doubtful than any of his Fatah colleagues currently out of jail can. He is the most able to reform the movement and make it more democratic. As importantly, he is fully supportive of the peace process and the two-state solution and has worked in the past with Israeli leaders to promote the peace process.”

Today Shikaki serves as director of the Ramallah-based Palestinian Center for Policy and Survey Research, which he has headed since 2000.